2022 IMS focuses on cutting-edge progress, explores precise diagnosis and treatment, and opens a new chapter in RRMM treatment with new therapies

On August 25-27, 2022, the 19th International Myeloma Society (IMS) annual meeting will be held in Los Angeles, California, USA.

MM is still an incurable and highly heterogeneous disease, and the survival outcomes of patients are affected by many factors, and there are often large differences

With the deepening of research, MM's risk stratification system is also constantly improving

The newly added 1q21+ in R2-ISS is a common karyotype abnormality in MM, and its incidence in Chinese patients is as high as 40%-60%.

So, could R2-ISS, which incorporates new adverse prognostic factors, be able to stratify MM patients more accurately than R-ISS? This was validated in a real-world study3 presented at the IMS Annual ^Meeting

The constantly updated risk stratification system provides a powerful "tool" for the precise diagnosis and treatment of MM, and individualized diagnosis and treatment is expected to become a new trend of development.

^{The treatment of RRMM has always been a hot topic of clinical attention, and the IMS annual meeting announced the latest progress of a number of studies: a large observational study4} including 5548 patients showed that 60%-90% of MM patients received multi-line 95.

For the selection of RRMM treatment options, a number of domestic and foreign guidelines recommend the use of CD38 monoclonal antibody combined with proteasome inhibitors and immunomodulators
.

Data from multiple studies have demonstrated the superiority of CD38 mAb, which also shows good efficacy and safety in high-risk MM patients
.

• Subgroup analyses of the CASTOR and POLLUX studies showed that daratumumab (Dara) combined with bortezomib, dexamethasone (DVd) and Dara combined with lenalidomide, dexamethasone (DRd) regimens were significantly better than Vd or Vd alone.
  Compared with Rd, the PFS and OS of RRMM patients with high risk, renal impairment, and advanced age (≥75 years) were significantly improved, and the PFS of patients with high cytogenetic risk was also significantly improved (HR=0.
  45; 95%CI, 0.
  31).
  -0.
  65) ⁵
  .
  
  In addition, Dara in combination with ixazomib, pomalidomide, and dexamethasone (DIPd), a well-tolerated quadruple regimen, demonstrated early safety in RRMM patients in a single-center phase II study and efficacy (median follow-up 15.
  1 months, median OS: 38.
  9 months, median PFS: 11.
  6 months; overall response rate [ORR]: 83%), and also showed benefit in patients with high cytogenetic risk trend ⁶
  .
  

• The latest data from the IKEMA study showed that the Isatuximab combined with carfilzomib and dexamethasone (Isa-Kd) regimen significantly improved the depth of remission in patients with RRMM compared with the Kd regimen (≥complete remission [CR] rate: 44.
  1% VS 28.
  5 %; minimal residual disease [MRD] negative rate: 33.
  5% vs 15.
  4%) ⁷ , for patients with high cytogenetic risk such as 1q21+, the Isa-Kd regimen (HR = 0.
  724; 95% CI, 0.
  361-1.
  451) improved Patient's PFS ⁸
  .
  
  In addition, interim analyses of real-world studies such as IONAMM and IMAGE confirmed the safety and efficacy of the Isa combination regimen in first-time relapse patients
  .
  
  

In addition to CD38, B cell maturation antigen (BCMA) is also a popular target for the treatment of MM
.

There are a variety of therapies targeting BCMA, including chimeric antigen receptor T cells (CAR-T), antibody drug conjugates (ADC), and bispecific antibodies for the treatment of RRMM
.

• Among them, CAR-T therapy has made great breakthroughs.
  This IMS annual meeting announced the phased results of the post-marketing real-world study of bb2121 (ide-cel).
  Currently, the median follow-up is 29 weeks, the ORR is 70%, the median PFS and OS were not achieved, and the efficacy and safety were comparable to clinical studies ⁹
  .
  
  

• Belantamab mafodotin, the world's first approved ADC targeting BCMA, is currently used for the fourth-line treatment of RRMM.
  The real-world study announced at this IMS annual meeting showed that the median follow-up was 11 months, and the median PFS was 4.
  7 months, The median OS was 14.
  5 months, and the safety profile was consistent with clinical trials ¹⁰
  .
  
  

• Teclistamab, a BCMA × CD3 bispecific antibody, was evaluated in the MajesTEC-1 study for safety and efficacy in patients with RRMM who received ≥3 lines of prior therapy including immunomodulators, proteasome inhibitors, and CD38 mAbs
  .
  
  Results presented at the IMS Annual Meeting showed that Teclistamab demonstrated superior OS and PFS benefits in patients with RRMM receiving ≥ 3 lines of prior therapy compared with real-world physician-chosen ^regimens11
  .
  
  

The efficacy of the nuclear export protein 1 (XPO1) inhibitor selinesol in RRMM is also of interest
.

A retrospective single-center study evaluating the efficacy of selinexole in the treatment of RRMM patients with high cytogenetic risk showed that compared with patients with other types of cytogenetic risk factors, selinexor was associated with del17p.
A better survival benefit was initially shown among patients (median follow-up: 6.
5 vs 7.
2 months; median OS: 10.
1 vs 8.
1 months; median PFS: 4.
2 vs 1.
4 months) ¹²
.

The survival outcome of MM patients is affected by many factors, and 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in MM, which has also been confirmed in Chinese patients
.

The R2-ISS, updated in May 2022, included 1q21+ and used a cumulative score to divide MM patients into four groups, a stratification system further validated by real-world studies
.

In addition to the improvement of the risk stratification system, many advances have been made in the treatment of RRMM.
The development of new drugs such as CD38 monoclonal antibody and BCMA-targeting CAR-T, ADC and bispecific antibodies provides more and more opportunities for RRMM patients.
Multiple treatment options
.

*Isatuximab is not yet approved in mainland China

MAT-CN-2219879

references:

[1] Rajkumar SV.
Am J Hematol.
2022 Aug;97(8):1086-1107.

[2] Chengcheng Fu, et al.
2022 IMS.
Abstract P063.

[3] Joanne Tan, et al.
2022 IMS.
Abstract P162.

[4] Arleigh McCurdy, et al.
2022 IMS.
Abstract P261.

[5] María-Victoria Mateos, et al.
2022 IMS.
Abstract P260.

[6] Anupama Kumar, et al.
2022 IMS.
Abstract P252.

[7] Roman Hajek, et al.
2022 IMS.
Abstract OAB-046.

[8] Ivan Spicka, et al.
EHA 2022; E-Poster EP981.

[9] Dalton Canonico, et al.
2022 IMS.
Abstract P006.

[10] Tamir Shragai, et al.
2022 IMS.
Abstract P114.

[11] Amrita Krishnan, et al.
2022 IMS.
Abstract P251.

[12] Hamid Ehsan, et al.
2022 IMS.
Abstract P242.

Click "Read the original text" to see more content